Temporal aspects of the epidemic of bovine spongiform encephalopathy in Great Britain: individual animal-associated risk factors for the disease

The objectives of this study were first to determine the cumulative incidence of bovine spongiform encephalopathy (BSE) in the British cattle population from July 1986 to June 1997, secondly, to identify individual animal-associated risk factors that influenced the age of onset of clinical signs in confirmed BSE cases, and, thirdly, to assess the effectiveness of the measures introduced to control BSE during the epidemic. The analyses were based on the population of British cattle at risk, derived from agricultural census data collected between 1986 and 1996, and BSE case data collected up to June 30, 1997. The unit of interest was individual adult cattle recorded on annual agricultural censuses between June 1986 and June 1996. Univariate and multivariate survival analysis techniques were used to characterise the age of onset of clinical signs. In total 167,366 cases of BSE were diagnosed in Great Britain up to June 30, 1997. The cumulative incidence of BSE between July 1986 and June 1997 was 1.10 (95 per cent confidence interval [CI] 1.09 to 1.10) cases per 100 adult cattle at risk. Cattle from the South east, South west and Eastern regions of England had 4.26 to 5.96 (95 per cent CI 4.15 to 6.14) times as great a monthly hazard of being confirmed with BSE as cattle from Scotland. Compared with cattle born before June 1985, those born between July 1987 and June 1988 had 22.5 (95 per cent CI 22.1 to 22.8) times the monthly hazard of being confirmed with BSE, whereas those born in the 12 months after July 1988 had only 7.39 (95 per cent CI 7.24 to 7.54) times the monthly hazard of being confirmed with BSE. This reduction in hazard was directly attributable to the ban on the use of ruminant protein as a feed instituted in July 1988. Successive cohorts from 1989 to 1991 experienced further reductions in the hazard of experiencing BSE. The additional decrease in hazard observed for the 1990 cohort may be attributed to the effect of the Specified Bovine Offal ban instituted in September 1990.     

BSE, feed and cattle in Switzerland: is there a spatial relation?

Cross-contamination of cattle feed with meat and bone meal (MBM) allowed in feed for other species is regarded as the current hypothesis for the infection pathway of Bovine Spongiform Encephalopathy (BSE) cases occurring after the implementation of a ban on feeding MBM to cattle. This study was aimed at establishing a spatial relation between BSE cases in Switzerland and the findings of MBM in cattle feed. A cluster analysis and a cohort study were performed. Two hundred sixteen BSE cases born after December 1990 and detected until August 1st 2005, screening data of 504 feed producers between 1996 and 2001 and population data from the Swiss 2001 cattle census were included. The cluster analysis showed feed producer, positive for MBM contaminations in cattle feed, as possible cluster centres for BSE cases. In the cohort study, farms within a radius of 2 and 10 km around positive feed producers showed significantly higher odds to have a BSE case than the control group. The odds ratio and its 95% confidence interval were 2.23 (1.26-3.93) for the 2 km radius and 1.38 (1-1.9) for the 10 km radius. The results provide evidence for a spatial relation between cross-contamination and BSE occurrence. These findings support the hypothesis of cross-contamination to be an important route for BSE transmission after a feed ban.     

Estimating the prevalence of BSE in dairy birth cohorts and predicting the incidence of BSE cases in Japan

Following the detection of the first case of BSE in Japan in September 2001, four million cattle were subjected to a rapid test for BSE up to the end of 2004. A further 10 cases were detected in the dairy cattle population and two cases in Holstein steers. We focused on the dairy population and estimated the prevalence of BSE infected animals within each birth cohort for the years 1992–2001 using Bayesian inference. From this we were able to predict historic and future trends in the number of infected animals culled from each cohort and whether or not they could be detected using a rapid test. Assuming that BSE infectivity entered Japan in 1995, 225 (95%CI: 111–418) infected animals were predicted to have been culled from 1995 to 2001, of which 116 (56–219) would have been slaughtered for human consumption, and 33 (12–65) cases would have been detected during this period if a BSE surveillance program as comprehensive as the one in place as of April 2004 was applied. Assuming that BSE infectivity entered Japan in 1992, 905 (366–4633) infected animals were predicted to have been culled from 1992 to 2001, of which 694 (190–2473) would have been slaughtered for human consumption, and 201 (53–693) cases would have been detected during this period. Assuming the April 2004 level of surveillance continues and that the feed ban introduced in 2001 is completely effective, 18 (3–111) BSE cases are likely to be detected in the future. The BSE epidemic in Japan most likely reached a peak between 1998 and 2001 and should be eradicated around 2012.     

Area-level risks for BSE in British cattle before and after the July 1988 meat and bone meal feed ban

In this paper we investigate area-level risk factors for BSE for the cattle population present in Great Britain between 1986 and 1997. By dividing this population into two birth cohorts, those born before the July 1988 ban on feeding ruminant-derived meat and bone meal to ruminants and those born after, second-order regional influences are distinguished from the strong first-order south-to-north gradient of area-level BSE risk using Bayesian hierarchical models that account for structured (spatially correlated) and unstructured heterogeneity in the data. For both cohorts area-level risk of BSE was increased by a more southerly location and greater numbers of dairy cattle, relative to non-dairy cattle. For the cohort of cattle born after the July 1988 ban on feeding ruminant-derived meat and bone meal area-level BSE risk was additionally associated with greater numbers of pigs, relative to cattle. These findings support the role of low level cross-contamination of cattle feed by pig feed as an influence on BSE incidence risk as the epidemic evolved. Prior to the 1988 meat and bone meal ban unexplained BSE risk was relatively uniformly distributed across the country whereas after the ban there were spatially aggregated areas of unexplained risk in the northern and eastern regions of England suggesting that local influences allowed BSE control measures to be less-successfully applied in these areas, compared with the rest of the country. We conclude that spatially localised influences were operating in divergent ways during the two phases of the epidemic.     

A spatio-temporal analysis of BSE cases born before and after the reinforced feed ban in France

A spatio-temporal analysis was carried out to see how the risk distribution of bovine spongiform encephalopathy (BSE) in France changed depending on the period of birth. The data concerned the 539 BSE cases born in France after the ban (BAB) of meat and bone meal (MBM) in 1990 and detected between July 1, 2001 and December 31, 2003, when the surveillance of BSE was comprehensive. Seventy-two of these cases were born after the reinforced (second) ban (BASB) in 1996, which involved the removal of BSE-risk materials and cadavers from the processing of MBM. The Ederer-Myers-Mantel (EMM) time and space cluster test was applied, after classifying the cases by trimester and region of birth, BAB or BASB status, and dairy or beef status. Then disease mapping was performed for four successive birth periods, three for the BAB cases (January 1991 through June 1994, July 1994 through June 1995, July 1995 through June 1996), and one for the BASB (July 1996 through October 1998). It was elaborated with the Bayesian graphical modelling methods and based on a Poisson distribution with spatial smoothing. The parameters were estimated by a Markov Chain Monte Carlo (MCMC) simulation method. The main finding was that the areas with the highest risk of BSE changed largely from one birth period to another; from the west, it reached the east of France for birth cohort 1994-1995 and the southwest for birth cohort 1995-1996. The EMM test identified a peak risk in this region both for dairy and beef cattle in the fall 1995. The spatial distribution of the risk for the BASB cases matched the spatial pattern of risk for the preceding BAB birth cohort quite well; this was in favour of a common origin of the infection of the BAB and BASB cases, despite the complementary control measures.     

Geographical clustering of cases of bovine spongiform encephalopathy (BSE) born in Switzerland after the feed ban

Over one-third of the cases of BSE in Switzerland have been born after the feed ban of December 1, 1990. Evidence for the geographical clustering of these cases emerged in two distinct regions. All the 354 BSE cases recorded until June 30, 2000 (set A), and the 376 cases recorded up to May 14, 2001 (set B), were georeferenced to the centres of the communities in which the herds of origin were located, and control populations were georeferenced to the centres of the communities in which these herds were located at the time of the census. The latitudes and longitudes of these centres were used in the statistical analysis of the spatial clustering. The Cuzick-Edwards test and the spatial scan statistics were applied to assess the significance of the clusters, while controlling for the spatial distribution of the underlying cattle population. There was global clustering of the cases born after the ban, and distinct and significant (P<0.05) spatial clusters were repeatedly identified in the two case datasets, and in several control populations (all cases born before the feed ban on a random sample of control farms) in terms of cattle density by region or cow density by region. Differential reporting was excluded as the underlying reason for the observed clusters.     

Cases of bovine spongiform encephalopathy born in Switzerland before and after the ban on the use of bovine specified risk material in feed

In Switzerland there was a reduction in the number of cases of bovine spongiform encephalopathy, observed in the birth cohorts from 1995 to 1996, but no further reduction in the following birth cohorts up to 1998. From the records of 34 cases born after April 30, 1996 (BAB96) and 174 cases born before April 30, 1996 and after December 1990 (BAB90), observed up to April 30, 2004, the risk factors at the farm level, possible routes of exposure and the geographical distribution of the cases were analysed to try to explain the observations. No evidence was found for a rate of exposure other than feed. There was some evidence that the risk factors at farm level were different between the BAB90 and BAB96 cases. A large proportion of the BAB96 cases was born in cantons that had reported only a few BAB90 cases, but a small cluster of the BAB96 cases was found in a region where there had been a cluster of BAB90 cases. The spatial distribution of these cases indicated that the risk of exposure to infection had been more randomly distributed than during the period up to April 1996. Farms with mixed livestock had a higher risk of having a case born after the ban on the feeding of specified risk material in 1996. In a regression model, a trend towards an association between cases of BSE and presence of small ruminants on the farm was observed for the BAB96 cases, and the presence of pigs and the pig:cattle ratio were significant for the BAB90 cases.     

Evaluation of the effectiveness of selected measures against bovine spongiform encephalopathy (BSE) in Switzerland by use of the basic reproduction ratio R0

The effectiveness of two measures against Bovine Spongiform Encephalopathy (BSE), the compulsory processing of animal by products to meat and bone meal (MBM) at 133 degrees C under 3 bars of pressure for 20 minutes in February 1993 and the exclusion of fallen stock, heads with eyes and spinal cord of cattle older than 30 month from MBM production in April 1996, was evaluated in a process model. The transmission of BSE by calculation of the basic reproduction ratio R0 was modelled.The results were verified by use of a cohort model, based on observed surveillance data. Prior to 1990, before the ban of feeding MBM to ruminants, R0, as calculated in the process model, was above 1, coherent with a slowly progressing BSE epidemic. Since 1991, values of R0 were low at 0.06.The corresponding R0 values derived from the cohort model were higher, the lowest value 0.13 calculated for 1996. Given such low R0 values, the epidemic should have died out. Additionally, no influence of the two measures was obvious at that time given the low level of R0. The discrepancy between the results of the two models is evidence for a dependency of the BSE epidemic from an infection source not considered in the process model. This infection source is most likely importation of feed ingredients and MBM.     

Epidemiological study on BSE outbreak in Japan

The aim of this study is to identify, as hypotheses, all feasible sources and routes of infection for the BSE cases in Japan, and to study the probability of each hypothesis. The strategy of this epidemiological study is as follows. 1) BSE risk status in Japan is tentatively divided into 3 stages, i.e., before 1996 April when administrative guidance for feed ban of cattle MBM introduced. After that to 2001 September, the first case of BSE in Japan, then, after 2001 October with real feed ban in the law. 2) Make hypotheses depending on the invasive risk scenarios and propagation risk of BSE in Japan, and they are checked by evidences, case control study or statistics. 3) Grouping of BSE cattle was conducted time sequentially and spatially; that is Group-A (1995-96, born in Hokkaido, Kanto), Group-B (1999 in Kyushu), Group-C (1999-2001 in Hokkaido), Group-D (young cattle born after real feed ban) and Pre-A, Post-D groups. As a result, a milk replacer was considered one of the most probable cause of group-A contamination, and group-C outbreak might be caused by an indigenous BSE propagation of group-A in Hokkaido. If the hypothesis of Holland animal fat as causative material was accepted, however, there are several unexplainable points. Collection of scientific evidences on animal fat impurity and age dependent susceptibility to BSE will be needed to clarify the true causative material.     

Updated prediction for the BSE epidemic in dairy cattle in Japan

Following the detection of the first case of Bovine spongiform encephalopathy (BSE) in Japan in September 2001, nine million cattle were tested for BSE up to the end of 2008. As a result, a further 28 cases were detected in dairy cattle. Using the mathematical model previously developed and surveillance data up to the end of 2008, we estimated the prevalence of BSE-infected animals within each birth cohort for the years 1995–2001. We predicted historic and future trends in the number of BSE-infected animals to be culled and anticipated BSE cases from each birth cohort. The results indicate that more infected animals (428 (95% CI: 59–727)) than previously estimated would have been culled from 1995 to 2001, and more cases (53 (95% CI: 25–101)) than previously predicted would have been detected during this period with a higher peak in 2001, if a BSE surveillance program as comprehensive as the present one was applied. In and after 2009, 0–2 cases of BSE would likely to be detected. As previously predicted, the BSE epidemic should be eradicated by 2012.     

Spatial heterogeneity of the risk of BSE in France following the ban of meat and bone meal in cattle feed

In France, meat-and-bone meal (MBM) has been prohibited for cattle feeding since 1990, but bovine spongiform encephalopathy (BSE) cases, called 'NAIF', appeared in animals born after this feed ban. Furthermore, in 1996 a new measure was taken: removal of cadavers and specified risk materials (SRM) from the processing of MBM dedicated to animal feed. Nevertheless, BSE cases (called 'super-NAIF') appeared in cattle born after this measure was in force. We analysed the spatial distribution of 445 'NAIF' and 58 'super-NAIF' cases detected in France from July 1, 2001 to July 31, 2003. The detection of BSE was based both on the mandatory reporting system (MRS) and the systematic test screening of cattle at the abattoir and at the fallen-animal plant with rapid tests. The background population was based on the adult-cow census. The disease mapping of the BSE risk was based on the standardised incidence ratio (stochastic Poisson process). A spatial component, which takes into account the spatial dependence between the geographical units by a notion of adjacency was used to eliminate the over-dispersion in the risk assessment. The geographical units were defined by hexagons with a side of 23km (France had 1264 hexagons). The parameters were estimated by a Metropolis Gibbs sampling algorithm using the Markov-chain Monte Carlo methods. The BSE cases were not randomly distributed. Furthermore, the areas at risk for the 'super-NAIF' matched part of the areas at risk for the 'NAIF' cases-which suggests that it might be a common source of contamination.     

Ten years of BSE in Switzerland. The development of an extraordinary disease

The first case of bovine spongiform encephalopathy (BSE) in Switzerland was diagnosed in November 1990. BSE is--in particular considering its eradication--different from many other livestock diseases. Strict disease control measures were taken from the very beginning by the Swiss authorities in order to protect public as well as animal health. In addition, BSE has stimulated enormous media interest and public concern. The occurrence of the born after the ban (BAB) cases, increasing questions about the zoonotic potential of the disease and trade restrictions against Switzerland led to the "BSE-crisis". In 1999, Switzerland internationally took a leading role in the surveillance of BSE by active investigation of targeted risk population.     

Simulating the BSE epidemic and multiplication factor in dairy herds in Japan

With the objective of evaluating the effectiveness of an administrative guidance on the use of ruminant meat-and-bone meal in ruminant feed, effective from April 1996 to September 2001, we developed a model to simulate the evolution of the BSE epidemic and to estimate the BSE multiplication factor (K) in the Japanese dairy population. The output that provided the best fit to the number of BSE cases both observed and predicted to date suggest that the probability that bovine MBM was fed back to cattle was 14.2-75.2% and 0.129-0.570% during the periods from 1992 to April 1996 and from April 1996 to October 2001, respectively. Given these estimates, the value of K would have peaked in 1995 at 40-48 and then declined to 0.32-0.67 between 1997 and 2001. These results suggest that the administrative guidance was effective in reducing the amount of MBM fed to cattle by a factor of 104-141 and was perhaps enough to drive the epidemic towards extinction.     

Spatial analysis of bovine spongiform encephalopathy in Galicia, Spain (2000-2005)

In Spain, the first bovine spongiform encephalopathy (BSE) case was detected in 2000 in a cow born in the Galicia region (Northwestern Spain). From then and until October 2005, 590 cases were detected, 223 of them in Galicia.

In 1994, meat and bone meal (MBM) was banned on ruminant feed and, in 1996, an EU decision mandating an overall change in MBM processing was implemented. This decision was gradually applied in the territory and not enforced before July 1998. The objective of this study was to explore clustering of BSE cases and estimate the standard incidence ratio (SIR) of BSE in Galicia. Our study was based on the BSE cases detected during the surveillance period 2000–2005 in the Galicia region. These cases were divided, based on birth date, into two periods: animals born from 1994 to July 1998, and those born after July 1998. We tested the role of cross-contamination on the geographical SIR distribution for both periods. Hierarchical Bayesian models were used to model the overdispersion and lack of independence of the SIR estimates. The geographical distribution of the standard incidence ratio of BSE between both periods was different. In the second period, the SIR was reduced in some areas. The reduction in these areas could be attributable to the changes in the processing of MBM. We did not find any statistical link between the poultry population and the standard incidence ratio, but pig population had a positive effect.     

A quantitative assessment of the risk of exposure to bovine spongiform encephalopathy via meat-and-bone meal in Japan

The feeding of meat-and-bone meal (MBM) derived from cattle infected with bovine spongiform encephalopathy (BSE) is a major source of BSE infection. The risks of BSE infection via MBM in Japan were examined quantitatively to estimate infectivity to cattle via MBM derived from a single clinically infected animal being rendered. Three routes of exposure were modeled: (i) feeding cattle concentrates containing MBM as an ingredient, (ii) feeding cattle concentrates contaminated with MBM from non-ruminant feed at feed plants and (iii) directly feeding MBM in supplemental form to cattle on farms. The effectiveness of measures designed to restrict the feeding of ruminants with ruminant MBM (feed restriction) as well as differences in the risk of exposure among regions were examined using the model.

The model revealed that the median total infectivity fed to dairy cattle via MBM derived from one infected animal was approximately 0.49 cattle oral ID₅₀ (5th percentile = 0.43 ID₅₀, 95th percentile = 0.54 ID₅₀). This value was reduced by 55% after the addition of MBM to cattle concentrates was restricted in 1996. The risk of exposure in dairy cattle was twice that in beef cattle. Comparisons of regional differences in exposure risk indicated that the risk was highest in a region where 14 of the 20 BSE cases reported to date were born. Our model suggested that the routes of exposure via MBM were unlikely to result in increased propagation of BSE in Japan. Furthermore, despite some regional variation, the risk of exposure declined further after the feed restriction was imposed in 1996.     

Imported and indigenous BSE cases in Germany

Bovine spongiform encephalopathy (BSE) is a transmissible fatal neurodegenerative disease in cattle with an average incubation time of five years. The first BSE case in an indigenous cow was detected in Germany in November 2000. This was almost eight years after the huge BSE epidemic in the United Kingdom had peaked, and several years after many EU member states had seen their first BSE case. In the 1990s, BSE had been diagnosed in six imported animals in Germany. However, after the implementation of an active surveillance programme using BSE rapid testing systems, 399 indigenous German BSE cases have been found up to the end of July 2006. The birth cohorts of 1995-1997 contribute to the vast majority of the first 250 German cases that were diagnosed between 2000 and 2003. However, the most recent German BSE cases belong primarily to the birth cohorts 1998-2000 which is indicative of a recycling of BSE infectivity at that time. Moreover, there were two BSE cases in cattle born in spring 2001, i.e. after the meat and bone meal feed ban had come into effect on 2nd December 2000. In this article, we describe the dynamics of the German BSE epidemic and compare these data with those of other countries that observed larger numbers of cases.     

BSE/TSE--the present epidemiologic and diagnostic situation

In 1992, 1994 and 1997, first BSE cases were diagnosed among imported cattle. The first domestic BSE case in Germany was confirmed on 26 November 2000. Altogether 192 cases (7 cases in 2000, 125 cases in 2001 and 60 cases in 2002) were reported (at the date: 7. August 2002). Comparing the BSE situation in Germany with other European countries under consideration of the surveillance schemes applied, Germany has a similar BSE incidence based on 100,000 adult cattle as France and Spain but a higher incidence than neighboring countries like The Netherlands, Austria and Denmark. At present, on average 2,3 cases per week are confirmed in Germany. With respect to the age distribution of the BSE cases, about 84% of all domestic cases confirmed originated out of the years 1995 and 1996 with a accumulation in 1996 (about 53% of all cases). Single BSE cases with the years of birth 1990, 1991 and 1993 demonstrate, that the BSE agent is circulating among the German cattle population at least since the beginning of the nineties. Between 1985 und 7 August 2002, scrapie was diagnosed in 26 sheep flocks in Germany, but alone during the year 2002 (until 7 August 2002) 11 scrapie affected sheep flocks were discovered.     

The price of the precautionary principle: Cost-effectiveness of BSE intervention strategies in the Netherlands

Since 1996, bovine spongiform encephalopathy (BSE) in cattle has been linked to a new variant of Creutzfeldt-Jakob disease (vCJD), a fatal brain disease in man. This paper assessed the cost-effectiveness of BSE control strategies instituted by the European Commission. In a Monte Carlo simulation model, a non-intervention baseline scenario was compared to three intervention strategies: removal of specified risk materials from slaughter animals, post-mortem testing for BSE and the culling of feed and age cohorts of BSE cases. The food risk in the baseline scenario ranged from 16.98 lost life years in 2002 to 2.69 lost life years in 2005. Removing specified risk materials removal practices, post-mortem testing and post-mortem testing plus cohort culling reduced this risk with 93%, 82.7% and 83.1%. The estimated cost-effectiveness of all BSE measures in the Netherlands ranged from 4.3 million euros per life year saved in 2002 to 17.7 million euros in 2005. It was discussed that the cost-effectiveness of BSE control strategies will further deviate from regular health economics thresholds as BSE prevalence and incidence declines.